Disease/Drug of interest:Schistosomiasis/Praziquantel (PZQ)
Motivation and Background:
Schistosomiasis, also known as bilharzia, is a disease caused by parasitic trematode blood flukes (schistosomes) that live in certain types of freshwater snails. When human skin comes in contact with contaminated water, the worms bury into it and take up residence in the body’s blood vessels.
Affecting almost 240 million people from 78 different countries worldwide, schistosomiasis leads as the second most catastrophic parasitic disease to date, yet is listed as one of the world’s Neglected Tropical Diseases (NTDs).
The disease dominates in rural areas of Africa, South America, and South Asia, and mainly affects people who live near large bodies of fresh water (lakes, rivers, canals, streams, etc.) and those who practice fishing, agriculture, or recreational swimming.
The most terrifying thing about schistosomiasis is how little is known about how it works. The target of PZQ, the most widely used drug for the treatment of schistosomiasis, is not known for certain. The drug was originally invented as a tranquilizer, but was found to be effective in the treatment of schistosomiasis. Eventually, schistosomes will become resistant to PZQ, which for now is our only efficient treatment against them. When this happens, we will have no back up plan. Therefore, it is essential that we develop a drug that is equivalent in cost efficiency, safety, and treatment efficiency to aid the millions of people still affected by Schistosomiasis today. Fig 1. Diagram depicting basic schistosome life cycle and how the parasite infects the host
Fig 2. Microscope view showing adult male schistosome S. mansoni worms before treatment with PZQ.
Target Information:
Size: molecular weight of the protein:
190 kDa
Location:
The mechanism of action for praziquantel (PZQ) remains unknown to this day. However, it is known that PZQ disrupts Ca2+ homeostasis in adult schistosomes by causing ion uptake, muscular contraction, and tegument disruption within seconds
Function in a normal cell:
Cav channels are widely suspected as the target due to their function. The channel opens when membrane potentials are depolarized, allowing calcium ions to flow down an electrochemical gradient (across the membrane). This causes calcium ion influxes that may trigger cellular excitation, including neuromuscular function (paralysis). The targets of praziquantel are therefore predicted to be voltage-gated calcium channels
Drug Information:
Schematic figure of drug:
Fig 3. Structural diagram of praziquantel anthelmintic Formula: C19H24N2O2EndFragment
Molecular weight: 312.411 g/molEndFragment
CAS Number: 55268-74-1EndFragment
Delivery method: Orally taken tablet Side effects: Side effects include tiredness, headaches, dizziness, nausea, upset stomach, mild fever, or mild skin rash.
Other names: Biltricide
Maker or company: Bayer
Is it patented? Bayer patented the drug in 1982 under the tradename “Biltricide”
Clinical Trials Info: In the early 1980s, clinical trials were conducted double-blindly for three common species of schistosomes.
Origin: The German company E. Merck, in search of a tranquilizer with minimal side effects, stumbled upon pyrazinoisoquinoline. The compounds proved to be ineffective tranquilizers so they were passed on to Bayer for veterinary screening, where the drug was discovered to be a very effective anthelminthic against a number of parasitic flukes and tapeworms.
Alternatives to this drug: Alternatives to PZQ include oxamniquine (a more expensive drug that restricts bioactivity of certain schistosome species) and hycanthone.
Miscellaneous: Today, Korea and China produce much of the raw materials associated with praziquantel, and the cost of production has dropped to just over 7 cents, making the possibility of widespread treatment even more realistic.
Other uses: This drug can be used to treat many types of blood flukes and tapeworms.
Disease/Drug of interest:Schistosomiasis/Praziquantel (PZQ)
Motivation and Background:
Schistosomiasis, also known as bilharzia, is a disease caused by parasitic trematode blood flukes (schistosomes) that live in certain types of freshwater snails. When human skin comes in contact with contaminated water, the worms bury into it and take up residence in the body’s blood vessels.
Affecting almost 240 million people from 78 different countries worldwide, schistosomiasis leads as the second most catastrophic parasitic disease to date, yet is listed as one of the world’s Neglected Tropical Diseases (NTDs).
The disease dominates in rural areas of Africa, South America, and South Asia, and mainly affects people who live near large bodies of fresh water (lakes, rivers, canals, streams, etc.) and those who practice fishing, agriculture, or recreational swimming.
The most terrifying thing about schistosomiasis is how little is known about how it works. The target of PZQ, the most widely used drug for the treatment of schistosomiasis, is not known for certain. The drug was originally invented as a tranquilizer, but was found to be effective in the treatment of schistosomiasis. Eventually, schistosomes will become resistant to PZQ, which for now is our only efficient treatment against them. When this happens, we will have no back up plan. Therefore, it is essential that we develop a drug that is equivalent in cost efficiency, safety, and treatment efficiency to aid the millions of people still affected by Schistosomiasis today.
Fig 1. Diagram depicting basic schistosome life cycle and how the parasite infects the host
References:
Schistosomiasis http://www.who.int/mediacentre/factsheets/fs115/en/ (accessed Feb 7, 2016).
Schistosomiasis FAQs http://www.cdc.gov/parasites/schistosomiasis/gen_info/faqs.html (accessed Feb 7, 2016).
Wang, H.; Fang, Z.-Z.; Zheng, Y.; Zhou, K.; Hu, C.; Krausz, K. W.; Sun, D.; Idle, J. R.; Gonzalez, F. J. Metabolic profiling of praziquantel enantiomers http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4168258/?tool=pmcentrez (accessed Feb 7, 2016).
External links:
http://www.webmd.com/drugs/2/drug-8873/praziquantel-oral/detailshttp://apps.who.int/medicinedocs/en/d/jwhozip48e/6.3.html
Fig 2. Microscope view showing adult male schistosome S. mansoni worms before treatment with PZQ.
Target Information:
Size: molecular weight of the protein:
190 kDaLocation:
The mechanism of action for praziquantel (PZQ) remains unknown to this day. However, it is known that PZQ disrupts Ca2+ homeostasis in adult schistosomes by causing ion uptake, muscular contraction, and tegument disruption within secondsFunction in a normal cell:
Cav channels are widely suspected as the target due to their function. The channel opens when membrane potentials are depolarized, allowing calcium ions to flow down an electrochemical gradient (across the membrane). This causes calcium ion influxes that may trigger cellular excitation, including neuromuscular function (paralysis). The targets of praziquantel are therefore predicted to be voltage-gated calcium channelsDrug Information:
Schematic figure of drug:
Fig 3. Structural diagram of praziquantel anthelmintic
Formula:
C19H24N2O2EndFragment
Molecular weight:
312.411 g/molEndFragment
CAS Number:
55268-74-1EndFragment
Delivery method: Orally taken tablet
Side effects:
Side effects include tiredness, headaches, dizziness, nausea, upset stomach, mild fever, or mild skin rash.
Other names:
Biltricide
Maker or company:
Bayer
Is it patented?
Bayer patented the drug in 1982 under the tradename “Biltricide”
Clinical Trials Info:
In the early 1980s, clinical trials were conducted double-blindly for three common species of schistosomes.
Origin:
The German company E. Merck, in search of a tranquilizer with minimal side effects, stumbled upon pyrazinoisoquinoline. The compounds proved to be ineffective tranquilizers so they were passed on to Bayer for veterinary screening, where the drug was discovered to be a very effective anthelminthic against a number of parasitic flukes and tapeworms.
Alternatives to this drug:
Alternatives to PZQ include oxamniquine (a more expensive drug that restricts bioactivity of certain schistosome species) and hycanthone.
Miscellaneous:
Today, Korea and China produce much of the raw materials associated with praziquantel, and the cost of production has dropped to just over 7 cents, making the possibility of widespread treatment even more realistic.
Other uses: This drug can be used to treat many types of blood flukes and tapeworms.